Abstract
Background
Global Initiative for Asthma (GINA) guidelines recommend a gradual step-down of asthma therapy if asthma has been well-controlled for at least 3 months. In real life, however, many well-controlled patients are prescribed high doses of inhaled corticosteroids (ICS), and are therefore unnecessarily at risk of systemic side effects associated with long-term ICS use. To encourage and facilitate step-down in a clinical setting, further pragmatic studies are required to demonstrate that good control of asthma can be maintained with a lower dose of ICS in stable and controlled patients, and to explore potential predictors for response to step-down.To test if good control of asthma can be maintained in adult patients previously stable on Flutiform® 250 (250 mcg fluticasone/10 mcg formoterol) for 12 weeks, after step-down to Flutiform® 125 (250 mcg fluticasone/5 mcg formoterol).
Methods
This was the second phase of a pragmatic, open-label, randomised controlled, non-inferiority trial in adult patients with asthma. Patients eligible for this phase had been on Flutiform® 250 for 12 weeks, had had no exacerbations during this period and were considered suitable for step-down by their GP. A total of 116 patients from 23 sites in the UK were randomised 1:1 to continue on Flutiform® 250 or to step down to Flutiform® 125. The primary outcome was asthma control assessed using the 7-item Asthma Control Questionnaire (ACQ7). Non-inferiority limit on the ACQ7 was set at 0.3. Patients were eligible for the non-inferiority analysis if they stayed on the randomised treatment for at least 8 weeks and did not change treatment before outcome visit. Secondary outcomes included forced expiratory volume in the first second (FEV1) % predicted, the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ), asthma control (according to GINA) and absence of exacerbations during outcome period. Analyses of secondary outcomes included all randomised patients [Full Analysis Set (FAS)]. Adherence was calculated based on dose counter values for patients who returned the study inhalers.
Results
Of the 107 patients who completed the study 48 (45%) were male and the mean [standard deviation (SD)] age was 54 (13) years. Of those randomised, 52 (90%) patients in each arm were eligible for the non-inferiority analysis (see figure for details of the FAS). At week 12, Flutiform® 125 was non-inferior to Flutiform® 250 in terms of asthma control assessed by ACQ7, with an upper confidence limit of 0.22, which is less than the pre-defined limit of 0.3 [mean difference 0.01; 95% confidence interval (CI), −0.20 to 0.22]. No significant differences between the groups were found for GINA asthma control, absence of exacerbations, Mini-AQLQ, or FEV1% predicted (see Table for treatment effect estimates). Adherence was high in both groups [median (inter-quartile range) 94% (88% to 106%) and 98% (77% to 103%) for the Flutiform® 125 and Flutiform® 250 groups, respectively] and there was no significant difference in distribution of adherence between the groups (P=0.20, Mann-Whitney U-test).
Conclusions
This study showed that real-life patients previously controlled on Flutiform® 250 can be stepped down to Flutiform® 125 and maintain good asthma control. Additional analyses are ongoing to investigate biomarkers [blood eosinophils, fractional exhaled nitric oxide (FeNO)] and other factors that might predispose patients to exacerbations or worsening of asthma control following ICS step-down. In the future, such predictors could help physicians to make more informed decisions on stepping down therapy in a real-life setting.
Keywords: Asthma, inhaled corticosteroids (ICS), flutiform